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A Screen Identifies the Oncogenic Micro-RNA miR-378a-5p as a Negative Regulator of Oncogene-Induced Senescence

Publikation: Forskning - peer reviewTidsskriftartikel

Dokumenter

Susanne Marije Kooistra, Lise Christine Rudkjær, Michael James Lees, Cornelia Steinhauer, Jens Vilstrup Johansen, Kristian Helin

Oncogene-induced senescence (OIS) can occur in response to hyperactive oncogenic signals and is believed to be a fail-safe mechanism protecting against tumorigenesis. To identify new factors involved in OIS, we performed a screen for microRNAs that can overcome or inhibit OIS in human diploid fibroblasts. This screen led to the identification of miR-378a-5p and in addition several other miRNAs that have previously been shown to play a role in senescence. We show that ectopic expression of miR-378a-5p reduces the expression of several senescence markers, including p16INK4A and senescence-associated β-galactosidase. Moreover, cells with ectopic expression of miR-378a-5p retain proliferative capacity even in the presence of an activated Braf oncogene. Finally, we identified several miR-378a-5p targets in diploid fibroblasts that might explain the mechanism by which the microRNA can delay OIS. We speculate that miR-378a-5p might positively influence tumor formation by delaying OIS, which is consistent with a known pro-oncogenic function of this microRNA.
OriginalsprogEngelsk
Artikelnummere91034
TidsskriftPloS one
Vol/bind9
Tidsskriftsnummer3
Sider (fra-til)1-7
Antal sider7
ISSN1932-6203
DOI
StatusUdgivet - 2014

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